Banxia Xiexin decoction alleviates N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric precancerous lesions by modulating the gastric microbiota.

BXD decreased pro-inflammatory cytokines and enhanced anti-inflammatory cytokine production in GPL mice.

• BXD intervention decreased TNF-α, IL-1β, and IL-6 levels in both gastric tissue and serum of GPL mice.
• BXD enhanced IL-10 production in GPL mice.
• These effects were assessed using ELISA in an MNNG-induced GPL mouse model.

BXD ameliorated intestinal metaplasia and suppressed proliferation and tumor suppressor markers in GPL mice.

• BXD ameliorated intestinal metaplasia as assessed by AB-PAS staining and H&E staining.
• BXD suppressed Ki67 expression, a marker of cell proliferation.
• BXD suppressed p53 expression in gastric tissue of GPL mice.
• These findings were evaluated using immunohistochemistry.

BXD mitigated gastric mucosal injury by upregulating tight junction and adhesion proteins.

• BXD upregulated the expression of Zonula occludens-1, E-cadherin, and Occludin.
• These proteins are associated with mucosal barrier integrity.
• Expression was assessed by Western blotting and immunofluorescence.

BXD inhibited the PI3K-Akt and MAPK signaling pathways in GPL mice.

• Network pharmacology was employed to analyze the underlying mechanisms of BXD in the treatment of GPL.
• Inhibition of PI3K-Akt and MAPK pathways was confirmed in both in vivo gastric tissue and in vitro GES-1 cell experiments.
• BXD protective effects against MNNG-induced GES-1 cells were also evaluated in vitro.

The gastric microbiota of GPL mice showed dysbiosis characterized by increased Bacillota and Proteobacteria at the phylum level.

• The gastric microbiota at the phylum level predominantly consisted of Bacillota, Proteobacteria, Cyanobacteria, Bacteroidota, Actinobacteria, Desulfobacterota, and Campylobacterota.
• In GPL mice, dysbiosis was notably marked by an increased presence of Bacillota and Proteobacteria.
• At the genus level, Lactobacillus and Streptococcus were significant contributors to GPL progression.
• Microbiota structure was assessed using 16S rRNA sequencing.

BXD intervention restored gastric microbiota balance by modulating the abundance of key bacterial genera.

• BXD restored gastric microbiota balance by enhancing Bacillota and Lactobacillus abundance.
• BXD reduced Proteobacteria and Streptococcus richness.
• These changes were identified through 16S rRNA sequencing analysis.

Lactobacillus intervention improved gastric mucosal pathology and modulated inflammation and barrier proteins in GPL mice.

• Lactobacillus treatment improved gastric mucosal atrophy and intestinal metaplasia associated with GPL.
• Lactobacillus intervention reduced levels of TNF-α, IL-1β, and IL-6 in gastric tissues while enhancing IL-10 production.
• Lactobacillus treatment promoted expression of Zonula occludens-1, E-cadherin, and Occludin.
• Lactobacillus inhibited activation of the PI3K-Akt and MAPK signaling pathways.
• These findings were validated through animal experiments.

Streptococcus intervention worsened gastric mucosal pathology and exacerbated inflammation and signaling pathway activation in GPL mice.

• Streptococcus treatment resulted in more severe gastric mucosal atrophy and intestinal metaplasia.
• Streptococcus treatment was marked by increased levels of TNF-α, IL-1β, and IL-6 and reduced IL-10 production.
• Streptococcus treatment showed no significant increase in the expression of Zonula occludens-1, E-cadherin, and Occludin.
• Streptococcus treatment enhanced activation of the PI3K-Akt and MAPK signaling pathways.
• These findings were validated through animal experiments.